This project examines the hypothesis that adenosine contributes to the physiological regulation of coronary blood flow. Studies in open-chest dogs show that changes in cardiac muscle adenosine content and reciprocal coronary resistance are closely dependent on changes in oxygen usage as the latter is perturbed experimentally over a five-fold range. Studies in enzymatically dispersed cardiocytes will examine the possibility that extracellular cyclic AMP rather than intracellular 5'-AMP is the precursor of cardiac adenosine.